Pharmacognostic Study on Elsholtzia ciliata (Thumb.) Hyl: Anatomy, Phytochemistry and Pharmacological Activities

Elsholtzia ciliata (Thunb.) Hyl, family Lamiaceae, is an important and popular anti-bacterial and anti-inflammatory Traditional Chinese Medicine (TCM). However, there are limited scientific studies on its anatomy and pharmacological activities. Moreover, the information of chemical constituents in relation to its non-volatile constituents are still missing. The current study aimed to evaluate the anatomic, pharmacological and phytochemical profile of Elsholtzia ciliata, providing means for the quality control of this herbal drug. The methodology designed for this study included the preparation of anatomic sections and their description, extraction, chromatography, structural elucidation of isolated compounds by NMR techniques and their quantification by HPLC using pharmacological assays (Formalin, hot plate, DPPH, antimicrobial-Gram positive, Gram Negative and fungus, and MTT assays) to confirm the activities described for this species. Results of the anatomic study are aligned with the pattern expected for plants belonging to the Lamiaceae family; Ursolic acid and Oroxylin were isolated from this plant species. The findings observed in this study indicate that Elsholtzia ciliata possess anti-inflammatory, antinociceptive, antioxidant, antimicrobial and anticancer activities. The chemical compounds isolated from its leaves and the anatomy profile of its parts provide the basis for further quality control for this plant.

New Nitrogenous Spongian Diterpenes from the New Zealand Marine Sponge Darwinella Oxeata

<p>During the course of this research five New Zealand marine sponges were investigated. Detailed examination of one of the species, Darwinella oxeata, has resulted in the isolation of ten compounds whose structures were elucidated using a variety of spectroscopic techniques and a simple derivatisation reaction. These compounds were identified as rearranged spongian diterpenes with the aplysulphurane backbone. Five of these compounds have been previously reported, though two of them were originally isolated from another marine sponge, Dendrilla membranosa. The five new compounds, oxeatamides C to G (25-29), were found to have the same diterpene portion as the oxeatamides already isolated from this sponge. They do, however, differ in the gamma-lactam side chain, which is proposed to be of amino acid origin. The new oxeatamides showed moderate levels of cytotoxicity against the HL-60 cell line in MTT assays.</p>

New Nitrogenous Spongian Diterpenes from the New Zealand Marine Sponge Darwinella Oxeata

<p>During the course of this research five New Zealand marine sponges were investigated. Detailed examination of one of the species, Darwinella oxeata, has resulted in the isolation of ten compounds whose structures were elucidated using a variety of spectroscopic techniques and a simple derivatisation reaction. These compounds were identified as rearranged spongian diterpenes with the aplysulphurane backbone. Five of these compounds have been previously reported, though two of them were originally isolated from another marine sponge, Dendrilla membranosa. The five new compounds, oxeatamides C to G (25-29), were found to have the same diterpene portion as the oxeatamides already isolated from this sponge. They do, however, differ in the gamma-lactam side chain, which is proposed to be of amino acid origin. The new oxeatamides showed moderate levels of cytotoxicity against the HL-60 cell line in MTT assays.</p>

Cdc25A inhibits autophagy-mediated ferroptosis by upregulating ErbB2 through PKM2 dephosphorylation in cervical cancer cells

Cervical cancer is the leading cause of cancer-related deaths in women, and treatment for cervical cancer is very limited. Emerging evidence suggests that targeting ferroptosis is a promising way to treat cancer. Here, we investigated the role of ferroptosis in cervical cancer, with a focus on the Cdc25A/PKM2/ErbB2 axis. Cervical cancer cells were treated with sorafenib to induce ferroptosis. Cellular MDA/ROS/GSH/iron detection assays were used to measure ferroptosis. MTT assays were performed to assess cell viability. qRT-PCR, western blot, and immunostaining assays were performed to measure the levels of proteins. Autophagy was monitored by fluorescence microscopy. Nuclear and cytosolic fractions were isolated to examine the location of PKM2 modifications. Co-IP experiments were conducted to determine the Cdc25A/PKM2 interaction. ChIP assays were performed to measure the binding affinity between H3K9Ac and the ErbB3 promoter, and a dual luciferase assay was performed to examine the transcriptional activity of ErbB2. A nude mouse xenograft model was used to examine the effects of the Cdc25A/ErbB2 axis on tumour growth in vivo. Cdc25A was elevated in human cervical cancer tissues but was reduced during sorafenib-induced ferroptosis of cervical cancer cells. Overexpression of Cdc25A inhibited sorafenib-induced ferroptosis by dephosphorylating nuclear PKM2 and suppressing autophagy. Cdc25A regulated autophagy-induced ferroptosis by increasing ErbB2 levels via the PKM2–pH3T11–H3K9Ac pathway. Cdc25A increased the resistance of cervical cancer to sorafenib, while knockdown of ErbB2 blocked these effects. Cdc25A suppressed autophagy-dependent ferroptosis in cervical cancer cells by upregulating ErbB2 levels through the dephosphorylation of PKM2. These studies revealed that Cdc25A/PKM2/ErbB2 pathway-regulated ferroptosis could serve as a therapeutic target in cervical cancer.

Calcium silicate-based cements affect the cell viability and the release of TGF-β1 from apical papilla cells

This study investigated the cytotoxicity and release of Transforming Growth Factor Beta 1 (TGF-β1) from cultured human apical papilla cells (APCs) after application of four bioactive materials. Culture of APCs was established and used for cytotoxic and quantitative assays. Extracts of Biodentine, Bio-C Repair, MTA Repair and White MTA were prepared and diluted (1, 1:4 and 1:16) and used for MTT assays up to 72 h. Total TGF-β1 was quantified by ELISA. Data were analyzed by ANOVA and Tukey’s test (α = 0.05). For Biodentine, at 24 h and 48 h, cell viability was lower than control (p < 0.05). At 72 h, only undiluted extract of Biodentine were cytotoxic (p < 0.05). At 24 h, a cytotoxic effect was found for undiluted and 1:4 dilution of Bio-C Repair (p < 0.05). At 48 h, however, Bio-C Repair at 1:4 and 1:8 dilution showed higher cell viability (p < 0.05). At 24 and 48 h, the cell viability for undiluted MTA Repair were higher than control (p < 0.05). For White MTA, at 24 and 48 h, all dilutions were cytotoxic (p < 0.05). All cements led to reduced release of total TGF-β1 from the APCs (p < 0.05). In conclusion, cell viability varied depending on the material and dilution. Only Bio-C repair and MTA repair led to higher cell viability of APCs. All materials induced a decrease in the release of total TGF-β1 from the APCs.

One-pot synthesis and biological evaluation of (2E,4E)-4-arylidene-2-styryl-5-oxopyrrolidine derivatives

Many marine alkaloids possess interesting structures and antitumor activities. Thus, we have synthesized (2 E,4 E)-4-arylidene-2-styryl-5-oxopyrrolidine derivatives of the marine alkaloids, rhopaladins A–D. The cytotoxicities of these derivatives against C-33A, CaSki, SiHa, HeLa, HepG2, and LO2 cells are evaluated by MTT assays. The results show that (2 E,4 E)-2-(4-chlorostyryl)-4-benzylidene- N-cyclohexyl-1-(4-fluorophenyl)-5-oxopyrrolidine-2-carboxamide significantly inhibits cancer cell proliferation, with IC50 values against C-33A, CaSki, SiHa, HeLa, and HepG2 cells of 5.56, 9.15, 12.5, 21.4, and 14.5 μM, respectively, and an IC50 value of 86.77 μM against the normal LO2 cell line.

Effects of Stryphnodendron adstringens extracts on murine 4T1 tumor line

Breast cancer appears as the main gynecological cancer and presents high morbidity and mortality. Because most diagnoses are made belatedly, it is necessary to seek therapeutic options that aim for advanced stages of the disease. This study aims to evaluate the antitumoral action of Stryphnodendron adstringens fruit extracts on 4T1 murine mammary carcinoma cell culture. The inhibitory potential of S. adstringens fruit extract on the metalloproteinases (MMPs) 2 and 9 was evaluated through zymography. From these results, MTT assays were performed to evaluate the extracts’ effects on the murine mammary carcinoma 4T1 line cell viability. From the crude extract, the following extracts were obtained: hydroalcoholic (SAFCEA), hexane (SAFCEB), chloroform (SAFCEC), and ethyl acetate (SAFCED). Lastly, the migration of the cells treated with extracts SAFCEA and SAFCED was verified. The hydroalcoholic extract (SAFCEA) was the most efficient in inhibiting gelatinases. During the phytochemical study, it was noted that alkaloids were present in all partitions. The 50 % growth inhibition (IC50) concentrations found were: 40.1 μg/mL (SAFCEA) and 70.14 μg/mL (SAFCED). After the cellular cytotoxicity assay, cell morphology was altered by treatment with the selected partitions (SAFCEA and SAFCED), obtaining morphology consistent with apoptosis. The results demonstrate that S. adstringens extracts exhibit the inhibitory activity of MMP-2 and MMP-9 as well as cytotoxicity toward 4T1 tumor cells. These findings indicate that follow-up studies of the partitions from S. adstringens may lead to the development of novel chemotherapeutics for oncological treatments.

Role of MicroRNA-101 on Proliferation and Migration of Prostate Cancer Cells

Background: MicroRNA-101 is a tumor inhibitor that stimulates tumor progression by reducing or inhibiting the expression of certain oncogenes. Some studies presented that cox-2 is target of MicroRNA 101 in prostate cancer process. Methods: MicroRNA-101 expression was detected by RT-PCR in PC3 cell lines. A and to determine cell proliferation we used MTT assays. Cell would heal and Flow cytometry assays were also used to detect cellular migratory ability and apoptosis, respectively. To assess cox-2 protein expression, Immunohistochemistry was used and data analyzed by data analysis by SPSS 20. Results: PC3 cells treated by MicroRNA-101 mimics displayed a 24% elevation in growth rate compared with blank (P < 0.01) at 48 h, and a 12% increase (P < 0.01) at 72 h. On the other hand, at 48 and 72 h after the MicroRNA-101 inhibitor transfection, proliferation of PC3 cell was decreased significantly. The early apoptosis rate in transfected PC3 cells with MicroRNA-101 mimic (74.4%) and inhibitor (22.8%) were significantly different at 72 h after transfection (P < 0.05), MicroRNA-101 mimics inhibited cell migration, adhesion, and spread was wider relative to the group of control and inhibitor for the PC3 cells. Expression of Cox-2 in transfected PC3 with the MicroRNA-101 inhibitor was higher than the mimic and control groups significantly (P < 0.01). Conclusion: MicroRNA-101 by Cox-2 can play key roles in the prostate cancer pathogenesis.

Hyaluronate-Thiol Passivation Enhances Gold Nanoparticle Peritumoral Distribution When Administered Intratumorally in Lung Cancer

Biofouling is the unwanted adsorption of cells, proteins, or intracellular and extracellular bio-molecules that can spontaneously occur on the surface of metal nanocomplexes. It represents a major issue in bioinorganic chemistry because it leads to the creation of a protein corona, which can destabilize a colloidal solution and result in undesired macrophage-driven clearance, consequently causing failed delivery of a targeted drug-cargo. Hyaluronic acid (HA) is a bioactive, natural mucopolysaccharide with excellent antifouling properties, arising from its hydrophilic and polyanionic characteristics in physiological environments which prevent opsonization. In this study, hyaluronate-thiol (HA-SH) (MW 10 kDa) was used to surface-passivate gold nanoparticles (GNPs) synthesized using a citrate reduction method. HA functionalized GNP complexes (HA-GNPs) were characterized using absorption spectroscopy, scanning electron microscopy, zeta potential, and dynamic light scattering. GNP cellular uptake and potential dose-dependent cytotoxic effects due to treatment were evaluated in vitro in HeLa cells using ICP-OES and Trypan blue and MTT assays. Further, we quantified the in vivo biodistribution of intratumorally injected HA functionalized GNPs in Lewis Lung carcinoma (LLC) solid tumors grown on the flank of C57BL/6 mice and compared localization and retention with nascent particles. Our results reveal that HA-GNPs show overall greater peritumoral distribution (**p&lt;0.005, 3 days post-intratumoral injection) than citrate-GNPs with reduced biodistribution in off-target organs. This property represents an advantageous step forward in localized delivery of metal nano-complexes to the infiltrative region of a tumor, which may improve the application of nanomedicine in the diagnosis and treatment of cancer.

Antineoplastic Activity of Rhus trilobata Nutt. (Anacardiaceae) against Ovarian Cancer and Identification of Active Metabolites in This Pathology

Rhus trilobata (RHTR) is a medicinal plant with cytotoxic activity in different cancer cell lines. However, the active compounds in this plant against ovarian cancer are unknown. In this study, we aimed to evaluate the antineoplastic activity of RHTR and identify its active metabolites against ovarian cancer. The aqueous extract (AE) and an active fraction (AF02) purified on C18-cartridges/ethyl acetate decreased the viability of SKOV-3 cells at 50 and 38 μg/mL, respectively, compared with CHO-K1 (>50 μg/mL) in MTT assays and generated changes in the cell morphology with apoptosis induction in Hemacolor® and TUNEL assays (p ≤ 0.05, ANOVA). The metabolite profile of AF02 showed a higher abundance of flavonoid and lipid compounds compared with AE by UPLC-MSE. Gallic acid and myricetin were the most active compounds in RHTR against SKOV-3 cells at 50 and 166 μg/mL, respectively (p ≤ 0.05, ANOVA). Antineoplastic studies in Nu/Nu female mice with subcutaneous SKOV-3 cells xenotransplant revealed that 200 mg/kg/i.p. of AE and AF02 inhibited ovarian tumor lesions from 37.6% to 49% after 28 days (p ≤ 0.05, ANOVA). In conclusion, RHTR has antineoplastic activity against ovarian cancer through a cytostatic effect related to gallic acid and myricetin. Therefore, RHTR could be a complementary treatment for this pathology.